(3S)-(−)9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid (levoflaxacin, LVFX: JP-A-62-252790, the term “JP-A” as used herein means an “unexamined published Japanese patent application.)
is known as an excellent synthetic antibacterial agent.
As intermediates in the production of this levofloxacin, compounds represented by formula (VI-a) (hereinafter referred to as compounds (VI-a); the same will apply to compounds represented by other formulae) are also useful:
(wherein X1 and X2, each independently represents a halogen atom).
As intermediates for racemic 9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid (oflxacin, OFLX):
compounds represented by formula (VI):
(wherein X1 and X2, each independently represents a halogen atom; and R5 and R6, each independently represents an alkyl group) are useful.
Conventional processes for producing the compound (VI-a) are as follows.

The production process reported by Japanese Patent No. 2,612,327 shown in the above figure suffers from a problem that epimerization arises under basic or acidic conditions and thus the yield of optically active (R)-NPNB is lowered.
In the process reported by Japanese Patent No. 2,771,871 which is a microbial reduction method, it is troublesome to purify the product since the physical properties of the product are not so largely different from those of the starting material.
Further, the process reported by Japanese Patent No. 2,573,269 leaves much to be improved as an industrial process, since an expensive asymmetric acyloxyboron alkali metal hydride is used therein as a reducing agent.
In the optical resolution method reported by JP-B-7-20946 (the term “JP-B” as used herein means an “examined Japanese patent publication), furthermore, it is needed to explore the reuse of the unnecessary isomer which is formed theoretically at a ratio of 50%.
The production process reported by U.S. Pat. No. 5,644,056 relates to a reaction of a racemate. To produce levofloxacin by this process, therefore, it is required to optically resolve the obtained product and the unnecessary isomer should be racemized or inverted. In addition, the specification of this patent discloses no experimental example of optically active compound.
The process reported by the Chinese document (Chinese Chemical Letters Vol. 6, No. 10, 857–860 (1995)) suffers from a problem that an additional step is needed for the deprotection of the p-toluenesulfonyloxy group used as a protective group.